Abstract
Phytosterols, which are derived from plants, have various beneficial physiological effects, including anti-hypercholesterolemic, anti-inflammatory, and antifungal activities. The anticancer activities of natural products have attracted great attention, being associated with a low risk of side effects and not inducing antineoplastic resistance. β-sitosterol, a phytosterol, has been reported to have anticancer effects against fibrosarcoma and colon, breast, lung, and prostate cancer. However, there are no reports of its activity against ovarian cancer. Therefore, we investigated whether β-sitosterol shows anticancer effects against ovarian cancer using human ovarian cancer cell lines. We confirmed that β-sitosterol induced the apoptosis of ovarian cancer cells and suppressed their proliferation. It triggered pro-apoptosis signals and the loss of mitochondrial membrane potential, enhanced the generation of reactive oxygen species and calcium influx through the endoplasmic reticulum-mitochondria axis, and altered signaling pathways in human ovarian cancer cells. In addition, we observed inhibition of cell aggregation, suppression of cell growth, and decreased cell migration in ovarian cancer cells treated with β-sitosterol. Further, our data obtained using ovarian cancer cells showed that, in combination with standard anti-cancer drugs, β-sitosterol demonstrated synergistic anti-cancer effects. Thus, our study suggests that β-sitosterol may exert anti-cancer effects against ovarian cancer in humans.
Highlights
Ovarian cancer originates in the ovary and invades the surrounding tissues, including the abdomen, lymph nodes, lungs, and liver
We investigated the cell state by annexin V and propidium iodide (PI) staining, to confirm the programmed cell apoptosis induced by β-sitosterol
Phytosterols are found in a various plants and have long been part of our diets. βPhytosterols are found in a various plants and have long been part of our diets. βsitosterol has been reported to have various physiological activities [6,7,8]
Summary
Ovarian cancer originates in the ovary and invades the surrounding tissues, including the abdomen, lymph nodes, lungs, and liver. Ovarian cancer is difficult to diagnose because in the early stages there are no visible symptoms, and only about 20% of ovarian cancers are detected early [1]. The overall five-year survival rate for ovarian cancer patients is 45%. In the USA [2]. There is a need for novel anticancer drugs without antineoplastic resistance or side effects to treat this condition. Ovarian cancer is a heterogeneous disease that includes several epithelial varieties with morphological and molecular subtypes, making effective treatments for specific types a necessity [3]. Ovarian cancer is divided into five categories: high- and low-grade serous, clear cell, endometrioid, and mucinous
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